Suppression of autophagy facilitates hydrogen gas-mediated lung cancer cell apoptosis
Leyuan Liu1, Zhenfeng Yan1, Yuanyuan Wang1
1Department of Respiration, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.
Abstract:
Our previous study found that hydrogen gas (H2) could efficiently inhibit lung cancer progression; however, the underlying mechanisms still remains to be elucidated. The present study aimed to explore the roles of H2 in lung cancer cell autophagy, and reveal the effects of autophagy on H2-mediated lung cancer cell apoptosis and the underlying mechanisms. The expression levels of proteins associated with cell apoptosis and autophagy were detected using western blot analysis. Cell autophagy was inhibited by 3-methyladenine treatment or Beclin1 downregulation, while rapamycin was used to induce autophagy. Cell growth and apoptosis were detected using the Cell Counting Kit-8 and flow cytometry assays, respectively. The results demonstrated that cell apoptosis and autophagy were significantly enhanced in the A549 and H1975 lung cancer cell lines treated with H2. However, autophagy enhancement weakened H2 roles in promoting cell apoptosis and vice versa. In addition, it was found that H2 treatment induced marked decreases in the protein expression levels of phosphorylated STAT3 and Bcl2, and overexpression of STAT3 abolished H2 roles in promoting cell apoptosis and autophagy. Overall, the present study revealed that H2 can promote lung cancer cell apoptosis and autophagy via inhibiting the activation of STAT3/Bcl2 signaling and suppression of autophagy can enhance H2 roles in promoting lung cancer cell apoptosis.
Insights
Hydrogen gas (H₂) enhances lung cancer cell apoptosis and autophagy by inhibiting STAT3/Bcl2 signaling. Suppressing autophagy boosts H₂
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Hydrogen gas (H₂) shows potential in inhibiting lung cancer progression.
- The precise mechanisms of H₂'s anti-cancer effects, particularly regarding autophagy and apoptosis, require further investigation.
Purpose of the Study:
- To investigate the role of H₂ in lung cancer cell autophagy.
- To elucidate the impact of autophagy on H₂-mediated apoptosis in lung cancer cells.
- To uncover the molecular mechanisms underlying these processes.
Main Methods:
- Western blot analysis to detect apoptosis and autophagy-related proteins.
- Pharmacological inhibition (3-methyladenine) and genetic downregulation (Beclin1) of autophagy.
- Autophagy induction using rapamycin.
- Cell Counting Kit-8 assay for cell growth.
- Flow cytometry for apoptosis detection.
Main Results:
- H₂ treatment significantly enhanced both apoptosis and autophagy in A549 and H1975 lung cancer cell lines.
- An inverse relationship was observed: enhanced autophagy attenuated H₂-induced apoptosis, and vice versa.
- H₂ decreased phosphorylated STAT3 and Bcl2 protein levels.
- STAT3 overexpression counteracted the pro-apoptotic and pro-autophagic effects of H₂.
Conclusions:
- H₂ promotes lung cancer cell apoptosis and autophagy by inhibiting the STAT3/Bcl2 signaling pathway.
- Inhibition of autophagy can potentiate the anti-cancer effects of H₂.
- These findings offer insights into novel therapeutic strategies involving hydrogen gas for lung cancer treatment.
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